Displaying publications 61 - 80 of 369 in total

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  1. Zowawi HM, Forde BM, Alfaresi M, Alzarouni A, Farahat Y, Chong TM, et al.
    Sci Rep, 2015;5:15082.
    PMID: 26478520 DOI: 10.1038/srep15082
    Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. Using Single Molecule Real Time (SMRT) sequencing we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. The precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Intriguingly, we identified three chromosomal copies of an ISEcp1-bla(OXA-181) mobile element, one of which has disrupted the mgrB regulatory gene, accounting for resistance to colistin. Our findings provide the first description of pandrug-resistant CRE at the genomic level, and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics.
  2. Ng KT, Takebe Y, Chook JB, Chow WZ, Chan KG, Abed Al-Darraji HA, et al.
    Sci Rep, 2015;5:15198.
    PMID: 26459957 DOI: 10.1038/srep15198
    Co-infections with human immunodeficiency virus type 1 (HIV-1) and human pegivirus (HPgV) are common in hepatitis C virus (HCV)-infected individuals. However, analysis on the evolutionary dynamics and transmission network profiles of these viruses among individuals with multiple infections remains limited. A total of 228 injecting drug users (IDUs), either HCV- and/or HIV-1-infected, were recruited in Kuala Lumpur, Malaysia. HCV, HIV-1 and HPgV genes were sequenced, with epidemic growth rates assessed by the Bayesian coalescent method. Based on the sequence data, mono-, dual- and triple-infection were detected in 38.8%, 40.6% and 20.6% of the subjects, respectively. Fifteen transmission networks involving HCV (subtype 1a, 1b, 3a and 3b), HIV-1 (CRF33_01B) and HPgV (genotype 2) were identified and characterized. Genealogical estimates indicated that the predominant HCV, HIV-1 and HPgV genotypes were introduced into the IDUs population through multiple sub-epidemics that emerged as early as 1950s (HCV), 1980s (HIV-1) and 1990s (HPgV). By determining the difference in divergence times between viral lineages (ΔtMRCA), we also showed that the frequency of viral co-transmission is low among these IDUs. Despite increased access to therapy and other harm reduction interventions, the continuous emergence and coexistence of new transmission networks suggest persistent multiple viral transmissions among IDUs.
  3. Chai KP, Othman NF, Teh AH, Ho KL, Chan KG, Shamsir MS, et al.
    Sci Rep, 2016 Mar 15;6:23126.
    PMID: 26975884 DOI: 10.1038/srep23126
    A new subfamily of glycosyl hydrolase family GH13 was recently proposed for α-amylases from Anoxybacillus species (ASKA and ADTA), Geobacillus thermoleovorans (GTA, Pizzo, and GtamyII), Bacillus aquimaris (BaqA), and 95 other putative protein homologues. To understand this new GH13 subfamily, we report crystal structures of truncated ASKA (TASKA). ASKA is a thermostable enzyme capable of producing high levels of maltose. Unlike GTA, biochemical analysis showed that Ca(2+) ion supplementation enhances the catalytic activities of ASKA and TASKA. The crystal structures reveal the presence of four Ca(2+) ion binding sites, with three of these binding sites are highly conserved among Anoxybacillus α-amylases. This work provides structural insights into this new GH13 subfamily both in the apo form and in complex with maltose. Furthermore, structural comparison of TASKA and GTA provides an overview of the conformational changes accompanying maltose binding at each subsite.
  4. Ser HL, Palanisamy UD, Yin WF, Chan KG, Goh BH, Lee LH
    Sci Rep, 2016 Apr 13;6:24247.
    PMID: 27072394 DOI: 10.1038/srep24247
    Actinobacteria from the unique intertidal ecosystem of the mangroves are known to produce novel, bioactive secondary metabolites. A novel strain known as MUSC 136(T) (=DSM 100712(T) = MCCC 1K01246(T)) which was isolated from Malaysian mangrove forest soil has proven to be no exception. Assessed by a polyphasic approach, its taxonomy showed a range of phylogenetic and chemotaxonomic properties consistent with the genus of Streptomyces. Phylogenetically, highest similarity was to Streptomyces misionensis NBRC 13063(T) (99.6%) along with two other strains (>98.9% sequence similarities). The DNA-DNA relatedness between MUSC 136(T) and these type strains ranged from 22.7 ± 0.5% to 46.5 ± 0.2%. Overall, polyphasic approach studies indicated this strain represents a novel species, for which the name Streptomyces malaysiense sp. nov. is proposed. The potential bioactivities of this strain were explored by means of antioxidant and cytotoxic assays. Intriguingly, MUSC 136(T) exhibited strong antioxidative activities as evaluated by a panel of antioxidant assays. It was also found to possess high cytotoxic effect against HCT-116 cells, which probably mediated through altering p53 protein and intracellular glutathione levels. Chemical analysis of the extract using GC-MS further affirms that the strain produces chemopreventive related metabolites.
  5. Chan XY, Hong KW, Yin WF, Chan KG
    Sci Rep, 2016 Jan 28;6:20016.
    PMID: 26817720 DOI: 10.1038/srep20016
    Tropical carnivorous plant, Nepenthes, locally known as "monkey cup", utilises its pitcher as a passive trap to capture insects. It then secretes enzymes into the pitcher fluid to digest the insects for nutrients acquisition. However, little is known about the microbiota and their activity in its pitcher fluid. Eighteen bacteria phyla were detected from the metagenome study in the Nepenthes pitcher fluid. Proteobacteria, Bacteroidetes and Actinobacteria are the dominant phyla in the Nepenthes pitcher fluid. We also performed culturomics approach by isolating 18 bacteria from the Nepenthes pitcher fluid. Most of the bacterial isolates possess chitinolytic, proteolytic, amylolytic, and cellulolytic and xylanolytic activities. Fifteen putative chitinase genes were identified from the whole genome analysis on the genomes of the 18 bacteria isolated from Nepenthes pitcher fluid and expressed for chitinase assay. Of these, six clones possessed chitinase activity. In conclusion, our metagenome result shows that the Nepenthes pitcher fluid contains vast bacterial diversity and the culturomic studies confirmed the presence of biocatalytic bacteria within the Nepenthes pitcher juice which may act in symbiosis for the turn over of insects trapped in the Nepenthes pitcher fluid.
  6. Goh SY, Khan SA, Tee KK, Abu Kasim NH, Yin WF, Chan KG
    Sci Rep, 2016;6:20702.
    PMID: 26860259 DOI: 10.1038/srep20702
    Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium.
  7. Law JW, Chan KG, He YW, Khan TM, Ab Mutalib NS, Goh BH, et al.
    Sci Rep, 2019 12 03;9(1):15262.
    PMID: 31792235 DOI: 10.1038/s41598-019-51622-x
    Streptomycetes have been the center of attraction within scientific community owing to their capability to produce various bioactive compounds, for instance, with different antimicrobial, anticancer, and antioxidant properties. The search for novel Streptomyces spp. from underexplored area such as mangrove environment has been gaining attention since these microorganisms could produce pharmaceutically important metabolites. The aim of this study is to discover the diversity of Streptomyces spp. from mangrove in Sarawak and their bioactive potentials - in relation to antioxidant and cytotoxic activities. A total of 88 Streptomyces isolates were successfully recovered from the mangrove soil in Kuching, state of Sarawak, Malaysia. Phylogenetic analysis of all the isolates and their closely related type strains using 16S rRNA gene sequences resulted in 7 major clades in the phylogenetic tree reconstructed based on neighbour-joining algorithm. Of the 88 isolates, 18 isolates could be considered as potentially novel species according to the 16S rRNA gene sequence and phylogenetic analyses. Preliminary bioactivity screening conducted on the potential novel Streptomyces isolates revealed significant antioxidant activity and notable cytotoxic effect against tested colon cancer cell lines (HCT-116, HT-29, Caco-2, and SW480), with greater cytotoxicity towards SW480 and HT-29 cells. This study highlighted that the Sarawak mangrove environment is a rich reservoir containing streptomycetes that could produce novel secondary metabolites with antioxidant and cytotoxic activities.
  8. Chua KO, Song SL, Yong HS, See-Too WS, Yin WF, Chan KG
    Sci Rep, 2018 Jul 17;8(1):10777.
    PMID: 30018403 DOI: 10.1038/s41598-018-29159-2
    The weaver ant Oecophylla smaragdina is an aggressive predator of other arthropods and has been employed as a biological control agent against many insect pests in plantations. Despite playing important roles in pest management, information about the microbiota of O. smaragdina is limited. In this work, a number of O. smaragdina colonies (n = 12) from Malaysia had been studied on their microbiome profile using Illumina 16S rRNA gene amplicon sequencing. We characterized the core microbiota associated with these O. smaragdina and investigated variation between colonies from different environments. Across all 12 samples, 97.8% of the sequences were assigned to eight bacterial families and most communities were dominated by families Acetobacteraceae and Lactobacillaceae. Comparison among colonies revealed predominance of Acetobacteraceae in O. smaragdina from forest areas but reduced abundance was observed in colonies from urban areas. In addition, our findings also revealed distinctive community composition in O. smaragdina showing little taxonomic overlap with previously reported ant microbiota. In summary, our work provides information regarding microbiome of O. smaragdina which is essential for establishing healthy colonies. This study also forms the basis for further study on microbiome of O. smaragdina from other regions.
  9. Ng KT, Chook JB, Oong XY, Chan YF, Chan KG, Hanafi NS, et al.
    Sci Rep, 2016 10 10;6:34855.
    PMID: 27721388 DOI: 10.1038/srep34855
    Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5'-UTR region showed high PCR efficiency (E = 99.6%, R2 = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2-7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control.
  10. Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.
    Sci Rep, 2020 Jan 10;10(1):319.
    PMID: 31924829 DOI: 10.1038/s41598-019-55964-4
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  11. Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.
    Sci Rep, 2019 02 28;9(1):3056.
    PMID: 30816228 DOI: 10.1038/s41598-019-39592-6
    A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name - Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA-DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03221T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.
  12. Liew KJ, Liang CH, Lau YT, Yaakop AS, Chan KG, Shahar S, et al.
    Sci Rep, 2022 Feb 18;12(1):2850.
    PMID: 35181739 DOI: 10.1038/s41598-022-06943-9
    The SKY hot spring is a unique site filled with a thick layer of plant litter. With the advancement of next-generation sequencing, it is now possible to mine many new biocatalyst sequences. In this study, we aimed to (i) identify the metataxonomic of prokaryotes and eukaryotes in microbial mats using 16S and 18S rRNA markers, (ii) and explore carbohydrate degrading enzymes (CAZymes) that have a high potential for future applications. Green microbial mat, predominantly photosynthetic bacteria, was attached to submerged or floating leaves litter. At the spring head, the sediment mixture consisted of plant debris, predominantly brownish-reddish gelatinous microbial mat, pale tan biofilm, and grey-white filament biofilm. The population in the spring head had a higher percentage of archaea and hyperthermophiles than the green mat. Concurrently, we cataloged nearly 10,000 sequences of CAZymes in both green and brown biofilms using the shotgun metagenomic sequencing approach. These sequences include β-glucosidase, cellulase, xylanase, α-N-arabinofuranosidase, α-L-arabinofuranosidase, and other CAZymes. In conclusion, this work elucidated that SKY is a unique hot spring due to its rich lignocellulosic material, often absent in other hot springs. The data collected from this study serves as a repository of new thermostable macromolecules, in particular families of glycoside hydrolases.
  13. Yaakop AS, Chan KG, Ee R, Lim YL, Lee SK, Manan FA, et al.
    Sci Rep, 2016 09 19;6:33660.
    PMID: 27641516 DOI: 10.1038/srep33660
    Jeotgalibacillus malaysiensis, a moderate halophilic bacterium isolated from a pelagic area, can endure higher concentrations of sodium chloride (NaCl) than other Jeotgalibacillus type strains. In this study, we therefore chose to sequence and assemble the entire J. malaysiensis genome. This is the first report to provide a detailed analysis of the genomic features of J. malaysiensis, and to perform genetic comparisons between this microorganism and other halophiles. J. malaysiensis encodes a native megaplasmid (pJeoMA), which is greater than 600 kilobases in size, that is absent from other sequenced species of Jeotgalibacillus. Subsequently, RNA-Seq-based transcriptome analysis was utilised to examine adaptations of J. malaysiensis to osmotic stress. Specifically, the eggNOG (evolutionary genealogy of genes: Non-supervised Orthologous Groups) and KEGG (Kyoto Encyclopaedia of Genes and Genomes) databases were used to elucidate the overall effects of osmotic stress on the organism. Generally, saline stress significantly affected carbohydrate, energy, and amino acid metabolism, as well as fatty acid biosynthesis. Our findings also indicate that J. malaysiensis adopted a combination of approaches, including the uptake or synthesis of osmoprotectants, for surviving salt stress. Among these, proline synthesis appeared to be the preferred method for withstanding prolonged osmotic stress in J. malaysiensis.
  14. See-Too WS, Ee R, Lim YL, Convey P, Pearce DA, Yin WF, et al.
    Sci Rep, 2017 02 22;7:42968.
    PMID: 28225085 DOI: 10.1038/srep42968
    Planococcus is a Gram-positive halotolerant bacterial genus in the phylum Firmicutes, commonly found in various habitats in Antarctica. Quorum quenching (QQ) is the disruption of bacterial cell-to-cell communication (known as quorum sensing), which has previously been described in mesophilic bacteria. This study demonstrated the QQ activity of a psychrotolerant strain, Planococcus versutus strain L10.15T, isolated from a soil sample obtained near an elephant seal wallow in Antarctica. Whole genome analysis of this bacterial strain revealed the presence of an N-acyl homoserine lactonase, an enzyme that hydrolyzes the ester bond of the homoserine lactone of N-acyl homoserine lactone (AHLs). Heterologous gene expression in E. coli confirmed its functions for hydrolysis of AHLs, and the gene was designated as aidP (autoinducer degrading gene from Planococcus sp.). The low temperature activity of this enzyme suggested that it is a novel and uncharacterized class of AHL lactonase. This study is the first report on QQ activity of bacteria isolated from the polar regions.
  15. Torres M, Hong KW, Chong TM, Reina JC, Chan KG, Dessaux Y, et al.
    Sci Rep, 2019 Feb 04;9(1):1215.
    PMID: 30718637 DOI: 10.1038/s41598-018-37720-2
    The Alteromonas stellipolaris strains PQQ-42 and PQQ-44, previously isolated from a fish hatchery, have been selected on the basis of their strong quorum quenching (QQ) activity, as well as their ability to reduce Vibrio-induced mortality on the coral Oculina patagonica. In this study, the genome sequences of both strains were determined and analyzed in order to identify the mechanism responsible for QQ activity. Both PQQ-42 and PQQ-44 were found to degrade a wide range of N-acylhomoserine lactone (AHL) QS signals, possibly due to the presence of an aac gene which encodes an AHL amidohydrolase. In addition, the different colony morphologies exhibited by the strains could be related to the differences observed in genes encoding cell wall biosynthesis and exopolysaccharide (EPS) production. The PQQ-42 strain produces more EPS (0.36 g l-1) than the PQQ-44 strain (0.15 g l-1), whose chemical compositions also differ. Remarkably, PQQ-44 EPS contains large amounts of fucose, a sugar used in high-value biotechnological applications. Furthermore, the genome of strain PQQ-42 contained a large non-ribosomal peptide synthase (NRPS) cluster with a previously unknown genetic structure. The synthesis of enzymes and other bioactive compounds were also identified, indicating that PQQ-42 and PQQ-44 could have biotechnological applications.
  16. Yong HS, Song SL, Chua KO, Wayan Suana I, Eamsobhana P, Tan J, et al.
    Sci Rep, 2021 May 21;11(1):10680.
    PMID: 34021208 DOI: 10.1038/s41598-021-90162-1
    Spiders of the genera Nephila and Trichonephila are large orb-weaving spiders. In view of the lack of study on the mitogenome of these genera, and the conflicting systematic status, we sequenced (by next generation sequencing) and annotated the complete mitogenomes of N. pilipes, T. antipodiana and T. vitiana (previously N. vitiana) to determine their features and phylogenetic relationship. Most of the tRNAs have aberrant clover-leaf secondary structure. Based on 13 protein-coding genes (PCGs) and 15 mitochondrial genes (13 PCGs and two rRNA genes), Nephila and Trichonephila form a clade distinctly separated from the other araneid subfamilies/genera. T. antipodiana forms a lineage with T. vitiana in the subclade containing also T. clavata, while N. pilipes forms a sister clade to Trichonephila. The taxon vitiana is therefore a member of the genus Trichonephila and not Nephila as currently recognized. Studies on the mitogenomes of other Nephila and Trichonephila species and related taxa are needed to provide a potentially more robust phylogeny and systematics.
  17. Tan JL, Simbun A, Chan KG, Ngeow YF
    Sci Data, 2020 05 05;7(1):135.
    PMID: 32371951 DOI: 10.1038/s41597-020-0475-x
    Mycobacterium tuberculosis (MTB) is commonly used as a model to study pathogenicity and multiple drug resistance in bacteria. These MTB characteristics are highly dependent on the evolution and phylogeography of the bacterium. In this paper, we describe 15 new genomes of multidrug-resistant MTB (MDRTB) from Malaysia. The assessments and annotations on the genome assemblies suggest that strain differences are due to lineages and horizontal gene transfer during the course of evolution. The genomes show mutations listed in current drug resistance databases and global MTB collections. This genome data will augment existing information available for comparative genomic studies to understand MTB drug resistance mechanisms and evolution.
  18. Liew YJM, Chua KO, Yong HS, Song SL, Chan KG
    Rev Bras Bot, 2022;45(4):1209-1222.
    PMID: 36320930 DOI: 10.1007/s40415-022-00845-w
    Boesenbergia rotunda (L.) Mansf. is a medically important ginger species of the family Zingiberaceae but its genomic information on molecular phylogeny and identification is scarce. In this work, the chloroplast genome of B. rotunda was sequenced, characterized and compared to the other Zingiberaceae species to provide chloroplast genetic resources and to determine its phylogenetic position in the family. The chloroplast genome of B. rotunda was 163,817 bp in length and consisted of a large single-copy (LSC) region of 88,302 bp, a small single-copy (SSC) region of 16,023 bp and a pair of inverted repeats (IRA and IRB) of 29,746 bp each. The chloroplast genome contained 113 unique genes, including 79 protein-coding genes, 30 transfer RNA (tRNA) genes and four ribosomal RNA (rRNA) genes. Several genes had atypical start codons, while most amino acids exhibited biased usage of synonymous codons. Comparative analyses with various chloroplast genomes of Zingiberaceae taxa revealed several highly variable regions (psbK-psbI, trnT-GGU-psbD, rbcL-accD, ndhF-rpl32, and ycf1) in the LSC and SSC regions in the chloroplast genome of B. rotunda that could be utilized as molecular markers for DNA barcoding and species delimitation. Phylogenetic analyses based on shared protein-coding genes revealed that B. rotunda formed a distinct lineage with B. kingii Mood & L.M.Prince, in a subclade that also contained the genera Kaempferia and Zingiber. These findings constitute the first chloroplast genome information of B. rotunda that could be a reference for phylogenetic analysis and identification of genus Boesenbergia within the Zingiberaceae family.

    SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40415-022-00845-w.

  19. Liu X, Wu Y, Chen Y, Xu F, Halliday N, Gao K, et al.
    Res. Microbiol., 2016 Apr;167(3):168-77.
    PMID: 26671319 DOI: 10.1016/j.resmic.2015.11.003
    The σ(S) subunit RpoS of RNA polymerase functions as a master regulator of the general stress response in Escherichia coli and related bacteria. RpoS has been reported to modulate biocontrol properties in the rhizobacterium Serratia plymuthica IC1270. However, the role of RpoS in the stress response and biofilm formation in S. plymuthica remains largely unknown. Here we studied the role of RpoS from an endophytic S. plymuthica G3 in regulating these phenotypes. Mutational analysis demonstrated that RpoS positively regulates the global stress response to acid or alkaline stresses, oxidative stress, hyperosmolarity, heat shock and carbon starvation, in addition to proteolytic and chitinolytic activities. Interestingly, rpoS mutations resulted in significantly enhanced swimming motility, biofilm formation and production of the plant auxin indole-3-acetic acid (IAA), which may contribute to competitive colonization and environmental fitness for survival. These findings provide further insight into the strain-specific role of RpoS in the endophytic strain G3 of S. plymuthica, where it confers resistance to general stresses encountered within the plant environment. The heterogeneous functionality of RpoS in rhizosphere and endophytic S. plymuthica populations may provide a selective advantage for better adaptation to various physiological and environmental stresses.
  20. Cheong HT, Ng KT, Ong LY, Chook JB, Chan KG, Takebe Y, et al.
    PLoS One, 2014;9(10):e111236.
    PMID: 25340817 DOI: 10.1371/journal.pone.0111236
    A novel HIV-1 recombinant clade (CRF51_01B) was recently identified among men who have sex with men (MSM) in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC) sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s) and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding the cross-border transmission of HIV-1 involving sexual networks is crucial for effective intervention strategies in the region.
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